spatial_genomics.md

1. Kacper A. Walentynowicz et. al. Single-cell genetic heterogeneity linked to immune infiltration in glioblastoma. Neuro-oncology, 2021

Protein expression of 79 markers were variable between cores from same tumor... Based on previous paper from Neftel et. al., amplification of EGFR, PDGFRA and CDK4 is associated with cancer cell states. The authors quantified their amplification using single cell FISH. PDGFRA showed no significant variations. Authors analyzed the frequency of cells in different tumors. The authors correlated proteins with the cell fractions, and found Olig2 was correlated with N/O cells (no amplification of either EGFR or CDK4)... The authors analyzed TERT mutation. In 50% cores (?not clear what is a core, seems just a ROI was regarded as a core) TERT were mutant. No correlation was found between hTERT promoter mutation and N/O cell frequency. Co-occurence stratified tumors in to EGFR & CDK4 co-occocure high (OR higi) high vs non-co-occure (OR low)tumors. ORhigh and ORlow had distent frequency of cell fractions and hTERT mutation.

ORhigh tumors were highly enriched in proteins associated with immune cell infiltration and immunosuppressive microenvironment.

2. Katherine et. al. Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response. Nature Cancer, 2021

pathological complete response (pCR) ~ cancer completely cured 28 patients pre-treatment, on-treatment and post-treatment (pCR or non-pCR), selected spatially distributed ROIs (cancer enriched/immune enriched). Validated in 29 independennt patients. individual DSP protein markers, including HER2 and CD45, did not significantly differ between pCR and non-pCR cases before treatment.

Cancer signaling and immune changes after short-term therapy.

Increased heterogeneity during HER2-targeted therapy.

DSP of tumor biopsies reveals features associated with pCR.

DSP predicts pCR in an independent validation cohort.

On-treatment CD45 IHC measurements are associated with pCR.

3. William et. al. Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatment. bioRxiv, 2020

4. Jessica et. al. Revisiting colorectal cancer tumorigenesis with spatially-resolved gene expression profiling. bioRxive, 2021

8 pT1 CRC samples x 9 ROIs

1. Spatially resolved gene expression profiling of the transcriptomic landscape of CRC tumorigenesis.

epithelial v.s. stromal, normal vs... samples of individual patiets did not form major clusters (tSNE) but histologuc features (nanostring CTA)

2. Biological processes associated CRC onset are distinct between epithelium and stroma.

Genes correlated with histologic pregresssion (how?) --> network analysis

3. Immune-related alterations 194 during CRC progression.

immune cell fraction (normal - carcinoma) --> immune-suppressed microvironment in tumor progression altered enrichment of WikiPathways focusing on the immune-related gene sets immunomodulatory gene expression related to anti-tumor immunity. Evasion of tumor destructuion by inhibition of phagocytosis.

4. Step-wise differential gene expression and biomarkers 256 of CRC tumorigenesis.

CTA RNA panel DEG, protein validated...